|Year : 2020 | Volume
| Issue : 2 | Page : 259-265
Comparison of blood-conserving and allogenic transfusion-sparing effects of antifibrinolytics in scoliosis correction surgery
Seshadri Ramkiran1, Mritunjay Kumar2, Lakshmi Krishnakumar3, Suresh G Nair4
1 Department of Anaesthesiology, Critical Care and Pain, Homi Bhabha Cancer Hospital and Research Centre, Vishakapatnam, Andhra Pradesh, India
2 Department of Anaesthesiology Pain Medicine and Critical Care, All India Institute of Medical Sciences, New Delhi, India
3 Department of Anesthesia and Critical Care, Amrita Institute of Medical Sciences, Kochi, Kerala, India
4 Department of Anesthesiology and Critical Care, Aster Medcity, Kochi, Kerala, India
|Date of Submission||23-Jun-2020|
|Date of Acceptance||01-Jul-2020|
|Date of Web Publication||12-Oct-2020|
Dr. Mritunjay Kumar
Department of Anaesthesiology Pain Medicine and Critical Care, All India Institute of Medical Sciences, Ansari Nagar, New Delhi - 110 029
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: Intraoperative antifibrinolytic drug administration is a safe and effective method of reducing blood loss and allogenic transfusions in patients undergoing spine deformity correction. Aim: This study aimed to compare the effectiveness of two antifibrinolytic drugs tranexamic acid (TXA) and epsilon amino caproic acid (EACA) in reducing peri-operative blood loss and transfusion requirements against a placebo control in patients with idiopathic scoliosis undergoing correction surgery. Setting and Design: This is a prospective, randomized, double-blinded, controlled comparative study. Methodology: Patients in TXA group received 50 mg.kg−1 bolus and 10 mg.kg−1.h−1 infusion as against 100 mg.kg−1 and 10 mg.kg−1.h−1 infusion in EACA group. The placebo group had saline bolus and infusion. Parameters observed included baseline demographic and deformity data, duration of surgery, total peri-operative blood loss, and allogenic packed red cell transfusion requirements. Statistical Analysis: Mean and standard deviation were used to represent the quantitative continuous data, and percentage was used to represent categorical data. The Student's t-test and ANOVA were used to compare means between groups. Bonferroni's multiple comparison test was used to find out the association between categorical variables. Results: A total of 36 patients were enrolled with 12 patients in each group. Peri-operative blood loss was 50.1% lower in patients receiving TXA and 17.7% lower in patients receiving EACA compared with the placebo group. The volume of total packed red cell transfusion was 66.7% lower in patients receiving TXA and 45.6% lower in patients receiving EACA compared with placebo. Conclusion: TXA was more effective in reducing total peri-operative blood loss and allogenic transfusion requirement in idiopathic scoliosis correction surgery compared to EACA.
Keywords: Allogenic transfusion, antifibrinolytics, epsilon amino caproic acid, scoliosis correction surgery, tranexamic acid
|How to cite this article:|
Ramkiran S, Kumar M, Krishnakumar L, Nair SG. Comparison of blood-conserving and allogenic transfusion-sparing effects of antifibrinolytics in scoliosis correction surgery. Anesth Essays Res 2020;14:259-65
|How to cite this URL:|
Ramkiran S, Kumar M, Krishnakumar L, Nair SG. Comparison of blood-conserving and allogenic transfusion-sparing effects of antifibrinolytics in scoliosis correction surgery. Anesth Essays Res [serial online] 2020 [cited 2020 Oct 26];14:259-65. Available from: https://www.aeronline.org/text.asp?2020/14/2/259/297827
| Introduction|| |
Perioperative blood loss continues to be a major concern in idiopathic scoliosis correction surgeries. Blood loss in such surgeries may sometimes exceed the estimated total blood volume requiring massive blood transfusion. Excessive blood loss increases the operative time and is associated with the risk of transfusion-related disease transmission; postoperative infections; and end-organ damage leading to increased morbidity, mortality, and length of hospital stay.,,, Among various factors, severe deformity, involvement of greater number of vertebrae, posterior approach for the surgery, neuromuscular involvement, intraoperative hypothermia, increased pressure in epidural venous plexuses, etc., have been found to be associated with increased blood loss during such surgeries. Consumptive and dilutional coagulopathy, factor deficiencies, clot dissolution, and increased fibrinolysis activation during massive blood loss are potential contributors to blood loss.,,, When intraoperative blood loss exceeds more than 50% of the total blood volume, circulating levels of coagulation factors diminish, further contributing to ineffective hemostasis.,
Although recent improvements in donor screening with effective testing have resulted in a many-fold decrease in transfusion-related disease transmission, the risk of transfusion-related viral and prion disease transmission, alloimmunization, graft versus host disease, transfusion-related acute lung injury and immunomodulation are still matters of concern.,,,,
As patients with scoliosis are subjected to multi-staged surgeries with exposure to many units of blood and blood components each time, efforts should be maximized to limit the transfusion units of blood products preventing alloimmunization to which a patient is exposed.,, Increased fibrinolysis is an important contributor for peri-operative blood loss in scoliosis surgery, which has led to the emergence of the role of antifibrinolytics in decreasing transfusion requirements during scoliosis, spine instrumentations and fusion surgeries.,,,,,,,
The last two decades has witnessed an upsurge in the use of antifibrinolytics for various surgical procedures for blood conservation, as well as the downfall of aprotinin as an antifibrinolytic due to its various adverse effects.,,,,,
In this study, we have evaluated and compared the efficacy of tranexamic acid (TXA) with that of epsilon amino caproic acid (EACA) using saline as a control, in reducing peri-operative blood loss and allogenic blood transfusion requirement in scoliosis surgery.
| Methodology|| |
This was a prospective, randomized, controlled, double-blind, comparative study conducted after institutional research ethics committee approval. Thirty-six patients of American Society of Anesthesiologists physical status I-III, of age group 7–18 years, belonging to either sex, with primary diagnosis of adolescent idiopathic scoliosis, were included in our study. Surgeries included were single-staged or multi-staged scoliosis correction by anterior or posterior approaches. Patients with bleeding diathesis, those with a history of thromboembolic episodes, those with preexisting renal disorders, those on chronic nonsteroidal anti-inflammatory drugs, and those with neuromuscular scoliosis were excluded from the study.
The patients enrolled in the study were randomly assigned to one of the three groups as follows:
- Group I: TXA group. Received TXA bolus dose of 50 mg.kg −1 immediate postinduction followed by 10 mg.kg −1/h infusion until wound closure
- Group II: EACA group. Received EACA bolus 100 mg.kg −1 immediate postinduction followed by 10 mg.kg −1.h −1 infusion until wound closure
- Group III: Placebo group. Received bolus of 10 mL.kg −1 saline immediate postinduction followed by 1 mL.kg −1.h −1 infusion.
Randomization and group allocation of patients were done by a computer-generated table and concealment by opaque sealed envelope, respectively. The bolus solution was prepared in a 100-mL 0.9% normal saline bottle followed by an infusion in a 50-mL syringe using a syringe pump. The rate of infusion was based on prefixed dose calculation handed over to the anesthesia technician, and the subsequent re-filling was done by the same technician who did not participate in any other phase of the study. Masking was ensured by using apparently identical saline bottles and syringes in all the three groups.
Anesthesia technique and performance
Written informed parental consent and patient's consent/assent for the surgery were taken. They were also explained about the intraoperative wake-up test. Intraoperative monitoring included 5-lead electrocardiography, invasive and noninvasive blood pressure, pulse-oximetry, end-tidal carbon dioxide, minimum alveolar concentration (MAC), nasopharyngeal temperature, urine output, central venous pressure (CVP), neuromuscular monitoring, and somatosensory-evoked potential (done by an electrophysiological assistant). After securing a large-bore intravenous (i.v.) cannula, anesthesia induction was done using i.v. glycopyrrolate 0.02 mg −1.kg −1, fentanyl 2 μg/kg, titrated dose of propofol up to 2 mg −1.kg −1, and atracurium 0.5 mg −1.kg −1. i.v. lignocaine 1.5 mg −1.kg −1 was given 45 s prior to intubation to attenuate laryngoscopy and intubation response. Oxygen and nitrous oxide combination was administered in low-flow, 50:50 ratio with sevoflurane not exceeding 1 MAC to facilitate neurological monitoring. Serial arterial blood gas (ABG) analysis was also done. Patients were positioned in prone or lateral position as per the requirement of the procedure, with adequate precautionary positioning measures such as eye-care and abdominal compression prevention. For patients undergoing scoliosis correction by anterior approach, a double-lumen tube was introduced by direct laryngoscopy or assisted by fiberoptic bronchoscope in order to facilitate lung isolation. Periodic intermittent continuous positive airway pressure application in nondependent lung and positive end-expiratory pressure in dependent lung were used to prevent atelectasis. Minute ventilation was targeted to achieve normocarbia. Normothermia was maintained by using convective hot air blankets with forced air warmer, prewarmed i.v. fluids, online fluid warmer for intraoperative infusion, and passive and active humidifiers.
Bolus dose of antifibrinolytic drugs or placebo was given well ahead of skin incision over 15 min. Infusion of the drugs or saline was continued till the end of the procedure. Nitroglycerine infusion was utilized, if needed to maintain mean arterial pressure (MAP) in the range of 55–65 mmHg intraoperatively. Surgical interventions included decortication of lamina, facet joints, and transverse process at each level and insertion of stabilizing rods with a de-rotation maneuver. Somatosensory-evoked potentials were monitored at each step, and the surgeons were informed in case of any discrepancy. Wake-up test was also done to confirm the adequacy of de-rotation maneuvers and to rule out any neurological deficits. An epidural catheter was introduced by the surgeon under direct vision, which was threaded out from the skin and attached to a filter ready for drug administration. An intercostal drain was left in situ at the site of pleural opening/tear. At the end of the procedure, the patients were turned supine and antifibrinolytic or saline infusion was stopped before shifting to the intensive care unit for elective ventilation.
Intraoperatively, i.v. fluids were administered as per the attending anesthesiologist's preference guided by MAP, CVP (target of 6–10 mmHg), urine output, and lactate levels. Blood transfusion was initiated upon blood loss exceeding 20%–30% of blood volume or if hematocrit <21% was recorded. Blood products such as fresh frozen plasma and platelet concentrates were transfused as per institutional policy or if >50% of blood volume was lost. Postoperatively, packed red cells were transfused if laboratory hemoglobin was below 7 g/dL. The exception to this rule was the presence of an active bleeding, hemodynamic instability, or any evidence of organ ischemia.
Estimation of blood loss was done by weighing sponges and quantifying suction bottles' volume after deduction of saline used and hemoglobin values in serial ABGs. In our study, large mops, medium sponges, and small gauzes were used, each with a dry weight of 25 g, 10 g, and 3 g, respectively. Blood loss on nonabsorbable surgical drapes and gown was not considered as it was difficult to quantify. Postoperatively, the total volume of blood collected in the surgical drain for 48 h was added in total blood loss.
The study sample size was determined to be 12 patients in each of the three groups, which provided 80% power for detecting a significant difference in total blood loss between the groups by at least 200 mL based on previous studies. Sample size calculations were done using nQuery Advisor® Version 7.0 (Statistical solution Ltd., Boston, MA, USA). Descriptive statistical tools such as mean and standard deviation were used to represent the quantitative continuous data, and percentage was used to represent categorical data. The Student's t-test was used both to assess homogeneity and to compare the main results and also to find difference between the groups for continuous variables. ANOVA was used to compare means between the three groups. Bonferroni's multiple comparison test was used to find out the association between categorical variables and post hoc analysis. For data which were not normally distributed and for evaluation at different time intervals, Kruskal–Wallis test was used and for skewed data Mann–Whitney test was used to determine interquartile range. Qualitative categorical data were analyzed using Chi-square test. In all cases, the level of statistical significance (P value) was 0.05. Data were analyzed using SPSS for Windows (version 23, SPSS, Chicago, IL, USA).
| Results|| |
Out of 36 patients included in this study, there were 30 girls and 6 boys, suggesting a predominance of adolescent idiopathic scoliosis among the female population [Figure 1]. There was no statistically significant difference in patients of the three groups with regard to demographics, preoperative laboratory parameters, ASA status, operative indications, and distribution of scoliosis severity [Table 1] and [Table 2].
|Table 1: Comparison of quantitative variables (mean±standard deviation) (ANOVA)|
Click here to view
The mean numbers of vertebrae fused, Cobb's angle, duration of surgery, surgical approach (25 posterior approach vs. 11 anterior approach), baseline parameters, and intraoperative hemodynamic variables in the form of MAP, CVP, urine output, core body temperature, and partial pressure of carbon-dioxide were also comparable among the groups [Table 3] and [Figure 2] and [Figure 3].
|Table 3: Factors influencing blood loss in our study as subgroup analysis (Kruskal-Wallis)|
Click here to view
|Figure 2: Comparison of intraoperative mean arterial pressure among the groups|
Click here to view
Use of both TXA and EACA resulted in significant reduction in perioperative blood loss compared to placebo group [Table 3]. Total perioperative blood loss was 874 ± 274 mL in the TXA group compared to 1442 ± 394 mL in the EACA group against that 1752 mL ± 335 mL in the saline group. Perioperative blood loss was 50.1% lower in patients receiving TXA compared with placebo, whereas it was 17.7% lower in patients receiving EACA compared to placebo [Figure 3] and [Figure 4] The total peri-operative blood loss was the summation of intraoperative blood loss and postoperative blood loss. The intraoperative blood loss was 46.5% lower in patients in the TXA group (592 mL) and 10.48% lower in the EACA group (991 mL) compared with the placebo group (1107 mL). The postoperative blood loss was 56.4% lower in patients in the TXA group (281 mL) compared with the placebo group (645 mL), whereas it was 30.08% lower in patients receiving EACA (451 mL) with respect to the placebo group [Figure 4].
Total packed red cell transfusion was 66.7% lower in patients receiving TXA (250 ± 152 mL) and 45.6% lower in patients receiving EACA (408 ± 207 mL) compared with the placebo group (750 ± 224 mL) [Figure 5]. We did not find any significant difference in the amount of fresh frozen plasma, crystalloids, colloid, and platelets transfused.
Intergroup comparison revealed that use of TXA caused a statistically significant reduction in total perioperative blood loss compared to the placebo group (P = 0.005). Reduction in total perioperative blood loss in EACA group was not statistically significant (P = 0.098). Similarly, transfusion requirement was significantly reduced in the TXA group when compared with the placebo group (P = 0.006) but not in the EACA group (0.883). Although use of EACA reduced perioperative blood loss and transfusion requirement when compared with placebo, it did not achieve statistical significance [Table 4] and [Figure 4] and [Figure 5]. On further analysis of factors, we found that surgery on >10.5 vertebral levels (P = 0.003) and surgery duration more than 5 h (P = 0.034) were associated with greater blood loss [Figure 6]. We did not find any significant association between blood loss and Cobb's angle [Figure 7].
|Table 4: Intergroup comparison for blood loss and transfusion (ANOVA and Bonferroni)|
Click here to view
|Figure 6: Comparison of total transfusion requirements among the groups (mL)|
Click here to view
| Discussion|| |
Scoliosis correction surgeries are associated with major blood loss for which various strategies such as preoperative autologous donation, hematinics and erythropoietin administration, acute normovolemic hemodilution, intraoperative cell salvage, and use of antifibrinolytics are practiced. Need for blood conservation and reduction in allogenic blood transfusion becomes paramount in scoliosis surgeries as most of these patients are subjected to multiple staged procedures.
TXA is a lysine analog that reversibly binds lysine receptor sites on plasminogen or plasmin to inactivate them, thus preventing fibrinolysis and protecting the clot and encouraging stasis., TXA has proven efficacy in reducing blood loss as well as transfusion requirements in spine surgeries for adolescent idiopathic scoliosis.,, Horrow et al. found that 10 mg.kg −1 was the minimum dose needed to obtain anti-hemorrhagic effect for TXA as per the pharmacologic dose–response trials. The suggested TXA dosing regimen for scoliosis surgery by Dell et al. and Neilipovitz et al. was 10 mg.kg −1 bolus followed by 1 mg.kg −1.h −1 infusion, but the optimal dose has not yet been established. Both high- and low-dose TXA dosing regimens have been used in pediatric patients undergoing spinal fusion for correction of idiopathic scoliosis and it varies from 10 mg.kg −1 bolus to 150 mg.kg −1.,, A 20 mg.kg −1 minimum dose of TXA has been recommended by a recent meta-analysis to decrease the total blood loss and intraoperative blood loss during scoliosis surgery., Johnson et al. reported that high-dose TXA (50 mg.kg −1) was more effective than low dose (10 mg.kg −1) in reducing blood loss and transfusion requirements in pediatric idiopathic scoliosis patients undergoing surgery. Similar dose has been used in other studies too.,, Dose–response trials on adults undergoing cardiac surgery have suggested that 70 mg.kg −1 TXA is more effective than 10 mg.kg −1 in one trial and a dose of 100 mg.kg − 1 was found to be more effective than 50 mg.kg −1 but equally effective to 150 mg.kg −1 in a second trial. Reid et al. used higher initial doses of TXA 100 mg.kg −1 followed by 10 mg.kg −1.h −1, which showed reduction in total blood loss by 24% and total transfusion volume by 38% in children undergoing repeat cardiac surgery. Sethna et al. also used the same 100 mg.kg −1 bolus followed by 10 mg.kg −1.h −1 in their study on pediatric patients undergoing scoliosis surgery and showed significant reduction in surgical blood loss during posterior spinal instrumentation by 41% compared with placebo. Sui et al. in their retrospective analysis stated that large-dose TXA (100 mg.kg −1 and 10 mg.kg −1.h −1 infusion) was effective and safe in reducing allogenic blood transfusion and blood loss in adolescent idiopathic scoliosis surgery.
We chose 50 mg.kg − 1 bolus followed by 10 mg.kg −1.h −1 TXA infusion as lower dose regimens are not as effective in reducing blood loss and transfusion requirements. Higher dose regimen of 50 mg.kg −1 was chosen instead of 100 mg.kg −1 because it offers no additional advantage in pharmacological dose response and limited reports of use of such dose in pediatric noncardiac surgery subsets.,,
Our study demonstrated that use of TXA led to 50% reduction in total blood loss compared to placebo (P = 0.005). Many previous studies have shown similar results. Sethna et al. documented a blood loss reduction by 41%, whereas Susan et al. demonstrated 27% reduction.
In our study, the total transfusion requirement was reduced by 500 mL in TXA group (250 mL vs. 750 mL in placebo), which was nearly 66% transfusion reduction (P = 0.006). Neilipovitz et al. showed 28% reduction in perioperative blood transfusions in TXA group in children undergoing scoliosis surgery, probably because of the lower dose regimen adopted (10 mg.kg−1 boluses +1 mg.kg−1.h−1). Similarly, 23% reduction in transfusion rate was demonstrable in the study by Bosch et al., whereas Alajmi et al. demonstrated 72.27% blood transfusion reduction by TXA in their study.
EACA has a very similar mechanism of action to reduce bleeding as that of TXA. The dosage of EACA chosen for our study was 100 mg.kg −1 bolus followed by 10 mg.kg −1.h −1 infusion, which was similar to the dose used by Florentino-Pineda et al., for scoliosis surgery and by Camarasa et al. for total knee replacement surgeries.
In our study, EACA use resulted in 17.7% reduction in total blood loss compared to placebo, which is clinically significant, but was not found to be statistically significant (P = 0.702). This result is comparable to the study by Florentino-Pineda et al., who used the same dosage on patients with idiopathic scoliosis and demonstrated total peri-operative blood loss reduction by 19%.
We did not observe any drug-related adverse events in our study. The incidence of hypercoagulation status has not been reported with either of the drugs in the dosages studied. Although intravascular thrombosis has been described in isolated nonsurgical case reports of patients receiving TXA for bleeding control, the actual incidence of vascular thrombosis has been reported to be very low in prospective controlled trials in children and adults.,,,,,,
Currently, there is no clinical evidence that the use of TXA increases the risk of thromboembolic events, namely myocardial infarction, stroke, deep-vein thrombosis, or pulmonary embolism as per many clinical trials as well as meta-analyses, and its safety has been well established.,,,,
A common misconception is that synthetic antifibrinolytics increase blood clotting. The drugs do not alter blood clotting but rather slow down the dissolution of blood clots. Hence, TXA and EACA can be safely used in patients undergoing scoliosis correction with a constant vigilance for deep-vein thrombosis.,,
Limitations of our study could be that a uniform stringent transfusion policy could not be strictly employed in our study. Need for transfusion was determined by the attending anesthesiologist depending on intraoperative hemodynamics and transfusion trigger of 7 g/dL. Second, TXA being 6–10 times more potent than EACA, dose equivalence could not be ensured in our study. Based on our study, we can make the following suggestions: (1) Continuation of antifibrinolytic infusion into postoperative period: Bleeding persists at a lower rate till 48 h after surgery, for which the antifibrinolytic infusion would be beneficial if extended postoperatively. (2) Each medical center must design its own blood salvage strategy taking into account the existing resources and specific circumstances and device individual practices to avoid allogenic transfusion risk using multimodality approach.
| Conclusion|| |
TXA is effective in reducing peri-operative blood loss and allogenic blood transfusions in idiopathic scoliosis corrective surgeries without significant side effects.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Karapurkar A, Kudalkar A, Naik L. Aprotinin, to reduce perioperative blood loss in scoliosis surgery. Indian J Anaesth 2002;46:378-80. [Full text]
Reid RW, Zimmerman AA, Laussen PC, Mayer JE, Gorlin JB, Burrows FA. The efficacy of tranexamic acid versus placebo in decreasing blood loss in pediatric patients undergoing repeat cardiac surgery. Anesth Analg 1997;84:990-6.
Dalmau A, Sabaté A, Acosta F, Garcia-Huete L, Koo M, Sansano T, et al
. Tranexamic acid reduces red cell transfusion better than epsilon-aminocaproic acid or placebo in liver transplantation. Anesth Analg 2000;91:29-34.
Karimi S, Lu VM, Nambiar M, Phan K, Ambikaipalan A, Mobbs RJ. Antifibrinolytic agents for paediatric scoliosis surgery: A systematic review and meta-analysis. Eur Spine J 2019;28:1023-34.
Neilipovitz DT, Murto K, Hall L, Barrowman NJ, Splinter WM. A randomized trial of tranexamic acid to reduce blood transfusion for scoliosis surgery. Anesth Analg 2001;93:82-7.
Pong RP, Leveque JC, Edwards A, Yanamadala V, Wright AK, Herodes M, et al
. Effect of tranexamic acid on blood loss, D-Dimer and fibrinogen kinetics in adult spinal deformity. J Bone Joint Surg Am 2018;100:758-64.
Bosch P, Kenkre TS, Soliman D, Londino JA, Novak NE. Comparison of the coagulation profile of adolescent idiopathic scoliosis patients undergoing posterior spinal fusion with and without tranexamic acid. Spine Deform 2019;7:910-6.
da Rocha VM, de Barros AG, Naves CD, Gomes NL, Lobo JC, Villela Schettino LC, et al
. Use of tranexamic acid for controlling bleeding in thoracolumbar scoliosis surgery with posterior instrumentation. Rev Bras Ortop 2015;50:226-31.
Urban MK, Beckman J, Gordon M, Urquhart B, Boachie-Adjei O. The efficacy of antifibrinolytics in the reduction of blood loss during complex adult reconstructive spine surgery. Spine (Phila Pa 1976) 2001;26:1152-6.
Dick AG, Pinder RJ, Lyle SA, Ember T, Mallinson C, Lucas J. Reducing allogenic blood transfusion in pediatric scoliosis surgery: Reporting 15 Years of a multi-disciplinary, evidence-based quality improvement project. Global Spine J 2019;9:843-9.
Laupacis A, Fergusson D. Drugs to minimize perioperative blood loss in cardiac surgery: Meta-analyses using perioperative blood transfusion as the outcome. The International Study of Peri-operative Transfusion (ISPOT) Investigators. Anesth Analg 1997;85:1258-67.
Schreiber GB, Busch MP, Kleinman SH, Korelitz JJ. The risk of transfusion-transmitted viral infections. The Retrovirus Epidemiology Donor Study. N Engl J Med 1996;334:1685-90.
Sazama K. Reports of 355 transfusion-associated deaths: 1976 through 1985. Transfusion 1990;30:583-90.
Florentino-Pineda I, Blakemore LC, Thomson GH, Kochert CP, Adler P, Tripi P. The effect of epsilon amino caproic acid on perioperative blood loss in patients with idiopathic scoliosis undergoing posterior spinal fusion. Spine 2001;26:1147-51.
Florentino-Pineda I, Thompson GH, Poe-Kochert C, Huang RP, Haber LL, Blakemore LC. The effect of amicar on perioperative blood loss in idiopathic scoliosis: The results of a prospective, randomized double-blind study. Spine (Phila Pa 1976) 2004;29:233-8.
McNicol ED, Tzortzopoulou A, Schumann R, Carr DB, Kalra A. Antifibrinolytic agents for reducing blood loss in scoliosis surgery in children. Cochrane Database Syst Rev 2016;9:CD006883.
Mangano DT, Tudor IC, Dietzel C, Multicenter Study of Perioperative Ischemia Research Group, Ischemia Research and Education Foundation. The risk associated with aprotinin in cardiac surgery. N Engl J Med 2006;354:353-65.
Mangano DT, Miao Y, Vuylsteke A, Tudor IC, Juneja R, Filipescu D, et al
. Mortality associated with aprotinin during 5 years following coronary artery bypass graft surgery. JAMA 2007;297:471-9.
Schouten ES, van de Pol AC, Schouten AN, Turner NM, Jansen NJ, Bollen CW. The effect of aprotinin, tranexamic acid, and aminocaproic acid on blood loss and use of blood products in major pediatric surgery: A meta-analysis. Pediatr Crit Care Med 2009;10:182-90.
Verma K, Errico TJ, Vaz KM, Lonner BS. A prospective, randomized, double-blinded single-site control study comparing blood loss prevention of tranexamic acid (TXA) to epsilon aminocaproic acid (EACA) for corrective spinal surgery. BMC Surg 2010;10:13.
Halanski MA, Cassidy JA, Hetzel S, Reischmann D, Hassan N. The Efficacy of Amicar Versus Tranexamic Acid in Pediatric Spinal Deformity Surgery: A Prospective, Randomized, Double-Blinded Pilot Study. Spine Deform 2014;2:191-7.
Khurana A, Guha A, Saxena N, Pugh S, Ahuja S. Comparison of aprotinin and tranexamic acid in adult scoliosis correction surgery. Eur Spine J 2012;21:1121-6.
Sui WY, Ye F, Yang JL. Efficacy of tranexamic acid in reducing allogeneic blood products in adolescent idiopathic scoliosis surgery. BMC Musculoskelet Disord 2016;17:187.
Yagi M, Hasegawa J, Nagoshi N, Iizuka S, Kaneko S, Fukuda K, et al
. Does the intraoperative tranexamic acid decrease operative blood loss during posterior spinal fusion for treatment of adolescent idiopathic scoliosis? Spine (Phila Pa 1976) 2012;37:E1336-42.
Horrow JC, Van Riper DF, Strong MD, Grunewald KE, Parmet JL. The dose-response relationship of tranexamic acid. Anesthesiology 1995;82:383-92.
Dell R, de-Ruiter J, Levino M, Mazzeo F. Does tranexamic acid decrease blood loss in children undergoing posterior spinal fusion for idiopathic scoliosis [abstract]. Can J Anaesth 1999; 46:A56.
Yuan QM, Zhao ZH, Xu BS. Efficacy and safety of tranexamic acid in reducing blood loss in scoliosis surgery: A systematic review and meta-analysis. Eur Spine J 2017;26:131-9.
Grant JA, Howard J, Luntley J, Harder J, Aleissa S, Parsons D. Perioperative blood transfusion requirements in pediatric scoliosis surgery: The efficacy of tranexamic acid. J Pediatr Orthop 2009;29:300-4.
Johnson DJ, Johnson CC, Goobie SM, Nami N, Wetzler JA, Sponseller PD, et al
. High-dose Versus Low-dose Tranexamic Acid to Reduce Transfusion Requirements in Pediatric Scoliosis Surgery. J Pediatr Orthop 2017;37:e552-7.
Zonis Z, Seear M, Reichert C, Sett S, Allen C. The effect of pre-operative tranexamic acid on blood loss after cardiac operations in children. J Thorac Cardiovasc Surg 1996; 111:982-7.
Goobie SM, Zurakowski D, Glotzbecker MP, McCann ME, Hedequist D, Brustowicz RM, et al
. Tranexamic Acid Is Efficacious at Decreasing the Rate of Blood Loss in Adolescent Scoliosis Surgery: A Randomized Placebo-Controlled Trial. J Bone Joint Surg Am 2018;100:2024-32.
Karski JM, Dowd NP, Joiner R, Carroll J, Peniston C, Bailey K, et al
. The effect of three different doses of tranexamic acid on blood loss after cardiac surgery with mild systemic hypothermia (32 degrees C). J Cardiothorac Vasc Anesth 1998;12:642-6.
Sethna NF, Zurakowski D, Brustowicz RM, Bacsik J, Sullivan LJ, Shapiro F. Tranexamic acid reduces intra-operative blood loss in pediatric patients undergoing scoliosis surgery. Anesthesiology 2005;102:727-32.
Alajmi T, Saeed H, Alfaryan K, Alakeel A, Alfaryan T. Efficacy of tranexamic acid in reducing blood loss and blood transfusion in idiopathic scoliosis: A systematic review and meta-analysis. J Spine Surg 2017;3:531-40.
Camarasa MA, Olle G, Serra-Prat M, Martin A, Sanchez M, Ricos P, et al
. Efficacy of amino caproic acid, tranexamic acid in the control of bleeding during total knee replacement: A randomized controlled clinical trial. Br J Anaesth 2006; 96:576-82.
Casati V, Bellotti F, Gerli C, Franco A, Oppizzi M, Cossolini M, et al
. Tranexamic acid administration after cardiac surgery: A prospective, randomized, double-blind, placebo-controlled study. Anesthesiology 2001;94:8-14.
Gruber EM, Shukla AC, Reid RW, Hickey PR, Hansen DD. Synthetic antifibrinolytics are not associated with an increased incidence of baffle fenestration closure after the modified Fontan procedure. J Cardiothorac Vasc Anesth 2000;14:257-9.
Benoni G, Fredin H, Knebel R, Nilsson P. Blood conservation with tranexamic acid in total hip arthroplasty: A randomized, double-blind study in 40 primary operations. Acta Orthop Scand 2001;72:442-8.
Sukeik M, Alshryda S, Haddad FS, Mason JM. Systematic review and meta-analysis of the use of tranexamic acid in total hip replacement. J Bone Joint Surg Br 2011;93:39-46.
Alshryda S, Sarda P, Sukeik M. Nargol A, Blenkinsopp J, Mason JM. Tranexamic acid in total knee replacement: A systematic review and meta-analysis. J Bone Joint Surg 2011;93:1577-85.
Shakur H, Roberts I, Bautista R, Caballero J, Coats T, Dewan Y, et al
. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): A randomised, placebo-controlled trial. Lancet 2010;376:23-32.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]
[Table 1], [Table 2], [Table 3], [Table 4]